Combining vitamin C with antibiotics destroys cancer stem cells

A combination of vitamin C and antibiotics could be key to killing cancer stem cells, a new study finds, paving the way for a strategy that could combat cancer recurrence and treatment resistance.

Researchers found that a therapy involving the antibiotic Doxycycline and ascorbic acid, or vitamin C, was up to 100 times more effective for killing cancer stem cells (CSCs) than 2-DG, a molecule currently being tested as an anti-cancer agent in clinical trials.

Study co-author Prof. Michael Lisanti, of the Biomedical Research Centre at the University of Salford in the United Kingdom, and colleagues recently reported their findings in the journal Oncotarget.

Stem cells are cells that have the ability to reproduce and transform into other cell types. Studies have suggested that some cancer cells act in a similar way to stem cells, reproducing in order to form and sustain tumors.

These CSCs are believed to be a main driver behind the growth, spread, and recurrence of tumors among patients with advanced cancer, and they also play a role in resistance to cancer therapy.

"Therefore, new therapeutic strategies are necessary to identify and eradicate CSCs," say Prof. Lisanti and colleagues.

With their new study, the researchers may have found a way to do just that.

A 'second punch' to kill CSCs

Earlier this year, Medical News Today reported on another study from Prof. Lisanti and team, in which they revealed how vitamin C is able to effectively kill CSCs.

The new study builds on those findings, showing that the CSC-killing capabilities of vitamin C can be increased with the help of antibiotics.

To reach their results, the researchers administered Doxycycline - an antibiotic used to treat acne, pneumonia, and other infections - to CSCs in increasing doses over 3 months.

The team explains that the antibiotic induces "metabolic flexibility," meaning that it inhibits the cells' ability to switch fuel sources as a means of survival. As a result, the cells are left with just glucose as a source of energy.

However, by following up Doxycycline administration with doses of vitamin C, the researchers were also able to remove glucose from CSCs - a "second punch" that effectively starves the cells to death.

"In this scenario, vitamin C behaves as an inhibitor of glycolysis, which fuels energy production in mitochondria, the 'powerhouse' of the cell," explains study co-author Dr. Federica Sotgia, also of the Biomedical Research Center at the University of Salford.

"Our results indicate that vitamin C it is a promising agent for clinical trials, and as an add-on to more conventional therapies, to prevent tumor recurrence, further disease progression, and metastasis."

Vitamin C and antibiotics: A new one-two 'punch' for knocking out cancer stem cells

Cancer stem cells, which fuel the growth of fatal tumours, can be knocked out by a one-two combination of antibiotics and Vitamin C in a new experimental strategy, published by researchers at the University of Salford, UK.

The antibiotic, Doxycycline, followed by doses of ascorbic acid (Vitamin C), were surprisingly effective in killing the cancer stem cells under laboratory conditions, according to the research published in the journal Oncotarget.

In boxing terms, this would be the equivalent of two blows delivered in rapid succession; a left-hand jab, followed by a right cross.

The researchers say their method offers a new explanation for how to prevent cancer cells from becoming treatment-resistant and how combinations therapies can be developed to overcome drug resistance.

Professor Michael Lisanti, who designed the study, explained: "We now know that a proportion of cancer cells escape chemotherapy and develop drug resistance; we established this new strategy to find out how they do it."

"We suspected the answer lay in the fact that certain cancer cells -- which we call metabolically flexible -- are able to switch their fuel source. Thus, when the drug treatment reduces the availability of a particular nutrient, the flexible cancer cells can feed themselves with an alternative energy source."

This new combination approach prevents cancer cells from changing their diet (metabolically inflexible), and effectively starves them, by preventing them from using any other available types of bio-fuels.

The team at the University of Salford's Biomedical Research Centre, added Doxycycline in ever increasing doses over a three-month period, to induce metabolic inflexibility. The result was to leave the cancer cells alive, but severely attenuated and depleted, so that they would be much more susceptible to starvation, by a second metabolic "punch."

First, the researchers inhibited the tumor cell mitochondria, by restricting the cancer cells only to glucose as a fuel source; then, they took away their glucose, effectively starving the cancer cells to death.

"In this scenario, Vitamin C behaves as an inhibitor of glycolysis, which fuels energy production in mitochondria, the "powerhouse" of the cell," explained co-author Dr Federica Sotgia.

The Salford team recently showed Vitamin C to be up to ten times more effective at stopping cancer cell growth than pharmaceuticals such as 2-DG, but they say that when Vitamin C is combined with an antibiotic, it is up to ten times more effective, making it nearly 100 times more effective than 2-DG.

As Doxycycline and Vitamin C are both relatively non-toxic, this could dramatically reduce the possible side-effects of anti-cancer therapy.

The Salford team also identified eight other drugs that could be used as a "second-punch" after the antibiotic regime, including berberine (a natural product) -- and a number of cheap non-toxic FDA approved drugs.

Professor Lisanti added: "This is further evidence that Vitamin C and other non-toxic compounds may have a role to play in the fight against cancer."

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